Significance: Proton therapy uses a precisely defined beam of penetrating charged particles to kill tumor cells, while sparing surrounding healthy tissues to a greater extent than is possible with conventional photon-based radiation therapy. To achieve this precision, verification that the treatment dose will be delivered precisely as specified is needed. Proton radiography is a promising way to verify correspondence between a modeled proton irradiation plan and observed proton radiation transport through patients. With proton radiography, precise correspondence between transmitted proton energy predictions and observations can validate treatment plans and enable reduced margins of safety for more precise dose delivery. Proton radiography imaging detectors have to date been impractical for use within the proton therapy clinical setting because of their bulk, cost, and difficulty of rapid electronic readout. We propose to use novel ultra-high-speed imaging detectors manufactured by our company to make a practical proton radiography system. Our system will be capable of measuring the time needed for a particle to travel at close to the speed of light over just inches with the required accuracy. With our detectors, we will measure proton energies using their speed for narrow, pulsed ?pencil beams? of protons with known energy. Monte Carlo-based treatment models will thereby be validated by comparing corresponding Monte Carlo-based transmission models with observed time-of-flight measurements. Hypothesis: We hypothesize that time-of-flight (and hence residual energy) predictions from Monte Carlo models for pencil-beam proton bunches which have traversed test ?phantom? objects will correspond with high precision to time-of-flight measurements performed using our new method. Preliminary Data: The response of our detector to similar particles has been measured, and we have modeled the expected response of our system to the slowed treatment protons that will traverse objects/patients and our proton radiography system. Specific Aims: This project will obtain proof-of-concept data to guide future radiography system designs. In Specific Aim 1, we will construct and test a portable test device for transport to a proton treatment beam. In Specific Aim 2, we will test and calibrate our system using protons of known energy, both without and then with known amounts of phantom material being traversed by the protons. In Specific Aim 3, we will computer model (simulate) both our Phase I measurements and those expected from a proposed Phase II proton radiography system consistent with our measurements, and will predict future systems? expected performance for patient-specific treatment plan verification within the clinical context.